Université d'Avignon et des Pays de Vaucluse, France.
ChemMedChem. 2010 Dec 3;5(12):2057-64. doi: 10.1002/cmdc.201000326.
The precise mechanism-of-action of thalidomide remains uncertain and might differ between diseases and under different clinical condition. With implications in the treatment of a variety of inflammatory and autoimmune diseases, as well as for use as an anticancer agent, alone or in combination with established therapeutics, it is clear that thalidomide and its derivatives deserve further scrutiny. In particular, thalidomide was shown to be effective in a mouse model of multiple sclerosis (MS), an autoimmune inflammatory disorder, called experimental autoimmune encephalomyelitis (EAE). Herein, we describe the synthesis and preliminary biological evaluation of new macromolecular prodrugs of thalidomide bearing an aminoalkyl group on the phthalimide ring. The effectiveness of these compounds to limit EAE was investigated, and it was shown that, at 100 mg kg⁻¹ thalidomide-equivalent dose, they abrogated the clinical and pathological features of EAE.
沙利度胺的作用机制尚不完全清楚，在不同疾病和不同临床情况下可能有所不同。由于沙利度胺在治疗各种炎症和自身免疫性疾病方面具有重要作用，并且可以单独或与已有的治疗方法联合用于癌症治疗，因此很明显，沙利度胺及其衍生物值得进一步研究。特别是，沙利度胺在多发性硬化症（MS）的小鼠模型中显示出有效性，MS 是一种自身免疫性炎症性疾病，称为实验性自身免疫性脑脊髓炎（EAE）。本文描述了在邻苯二甲酰亚胺环上带有氨基烷基的新型大分子沙利度胺前药的合成及初步生物学评价。研究了这些化合物对限制 EAE 的有效性，结果表明，在 100mg/kg 沙利度胺等效剂量下，它们可消除 EAE 的临床和病理特征。
